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Review
. 2021 Aug 18:14:17562864211039648.
doi: 10.1177/17562864211039648. eCollection 2021.

Multiple Sclerosis Therapy Consensus Group (MSTCG): position statement on disease-modifying therapies for multiple sclerosis (white paper)

Affiliations
Review

Multiple Sclerosis Therapy Consensus Group (MSTCG): position statement on disease-modifying therapies for multiple sclerosis (white paper)

Heinz Wiendl et al. Ther Adv Neurol Disord. .

Abstract

Multiple sclerosis is a complex, autoimmune-mediated disease of the central nervous system characterized by inflammatory demyelination and axonal/neuronal damage. The approval of various disease-modifying therapies and our increased understanding of disease mechanisms and evolution in recent years have significantly changed the prognosis and course of the disease. This update of the Multiple Sclerosis Therapy Consensus Group treatment recommendation focuses on the most important recommendations for disease-modifying therapies of multiple sclerosis in 2021. Our recommendations are based on current scientific evidence and apply to those medications approved in wide parts of Europe, particularly German-speaking countries (Germany, Austria, and Switzerland).

Keywords: disease-modifying therapy; guideline; multiple sclerosis; treatment recommendation.

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Conflict of interest statement

Conflict of interest statement: The authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: H.W.: Received grants or contracts from BMBF, Novartis, Genzyme, Roche, Merck, Biogen, DFG, European Union; royalties or licenses from Hogrefe, Springer Medizin; Consulting fees from Merck, Novartis, Roche, Sanofi; payment for expert testimony AXA banque patrimoniale, Dialectica, Swiss MS society, Peervoice; support for attending meetings and/or travel from Biogen, FEO, Merck, Novartis, Pfizer, Sanofi, Celgene, Excell/Bial, Roche. Participation on a Data Safety Monitoring Board or Advisory Board for PSI CRO Germany. R.G.: Received grants or contracts from Novartis, Biogen, Sanofi; consulting fees from Merck Serono, Janssen, Biogen, Novartis, Sandoz; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from BayerVital, Biogen, Eisai, Bristol Myers Squibb, TEVA, Merck Serono, Novartis, Roche, Sanofi-Aventis. Participation on a Data Safety Monitoring Board or Advisory Board for Roche, Genentech; Leadership or fiduciary role in other board, society, committee or advocacy group, paid or unpaid as Chair of DMSG Medical Advisory Board (honorary position). Has stock or stock options for Roche, Bayer, Merck. R.G. is the Editor-in-Chief of Therapeutic Advances in Neurological Disorders, therefore, the peer-review process was managed by alternative members of the board and the submitting editor was not involved in the decision-making process. T.B.: Received grants or contracts from Austrian MS Society, Austrian Research Fund, Austrian National Bank, Austrian Society of Neurology and from Alexion, Biogen, Merck, Novartis, Roche Sanofi-Genzyme; consulting fees from Biogen, Bionorica, MedDay, Merck, Novartis, Roche, Sanofi-Genzyme; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Allergan, Biogen, Biologix, Bionorica, Celgene/BMS, MedDay, Merck, Novartis, Roche, Sanofi-Genzyme, TEVA. Leadership or fiduciary role in other board, society, committee or advocacy group, paid or unpaid as President Austrian Society of Neurology (unpaid), President of the Austrian MS Research Society (unpaid), Chair of Scientific Committee, and Board Member of the European Academy of Neurology (unpaid). T.D.: Received grants or contracts from Alexion, Biogen, Roche; consulting fees from Alexion, Biogen, Celgene, Geneuro, Novartis, Roche, Sanofi, Merck; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Alexion, Biogen, Celgene, Novartis, Roche, Sanofi, Merck. Participation on a Data Safety Monitoring Board or Advisory Board for Roche, Polyneuron, MedDay, Alexion, Biogen, Celgene, Novartis, Roche, Sanofi, Merck. Leadership or fiduciary role in other board, society, committee or advocacy group, paid or unpaid as Executive board member of ECTRIMS (unpaid). Other financial or non-financial interests that is, my wife is an employee of Novartis and holds shares from Novartis. R.L.: Received grants or contracts from Novartis; consulting fees from Biogen, Celgene/BMS, Janssen, Merck, Novartis, Roche; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Celgene/BMS, Merck, Novartis, Roche, Sanofi-Genzyme. Participation on a Data Safety Monitoring Board or Advisory Board for Novartis, Celgene; Leadership or fiduciary role in other board, society, committee or advocacy group, paid or unpaid as Beisitzer Vorstand KKMMS, Stv. Vorsitz ÄB DMSG. M.M.: Received grants or contracts from Merck; consulting fees from Biogen, Bayer, Janssen, Celgene, Merck, Novartis, Roche, Sanofi-Genzyme; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Biogen, Bayer, Janssen, Celgene, Merck, Novartis, Roche, Sanofi-Genzyme. O.A.: Received grants or contracts from Biogen, Merck, Novartis, Roche; Consulting fees from Biogen, Celgene, Merck, Novartis, Roche; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Almirall, Biogen, Merck, Novartis, Roche, Sanofi, Teva; support for attending meetings and/or travel from Biogen, Merck, Roche. K.B.: Declares that there is no conflict of interest. M.B.: Received grants or contracts from Novartis; consulting fees from Sanofi-Aventis Dtl. GmbH, Novartis Pharma GmbH, Janssen-Cilag GmbH, Roche Pharma AG, Merck Serono GmbH, Biogen GmbH; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Sanofi-Aventis Dtl. GmbH, Novartis Pharma GmbH, Roche Pharma AG, Alexion Pharma GmbH, Merck Serono GmbH; support for attending meetings and/or travel from Celgene GmbH, Biogen GmbH, Novartis Pharma GmbH. S.B.: Received payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Biogen-Idec, Bristol Meyer Squibbs, Merck Serono, Novartis, Roche and Sanofi-Genzyme; support for attending meetings and/or travel from Merck Serono. A.Ch.: Received grants or contracts from EU (Horizon 2020 research grant), EU (Marie-Curie network initiative), Swiss national foundation, Swiss MS Society; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Actelion-Janssen, Almirall, Bayer, Biogen, Celgene, Sanofi-Genzyme, Merck, Novartis, Roche, Teva; support for attending meetings and/or travel from Actelion-Janssen, Almirall, Bayer, Biogen, Celgene, Sanofi-Genzyme, Merck, Novartis, Roche, Teva. Participation on a Data Safety Monitoring Board or Advisory Board for Sanofi-Genzyme, Biogen, Merck; Leadership or fiduciary role in other board, society, committee or advocacy group, paid or unpaid as Swiss MS Society Board member, Swiss MS Society Member of medicoscientific advisory board, German MS Society Member of ärztlicher Beirat. Receipt of equipment, materials, drugs, medical writing, gifts, or other services from Sanofi-Genzyme, Biogen, Merck. Other financial or non-financial interests, that is, European Journal of Neurology Associate editor, Clin Transl Neurosci Editorial board, J Int Med Res Editorial board. A.Cz.: Received consulting fees from Biogen, Celgene, Novartis, Roche, Almirall, Merck, TEVA; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Biogen, Celgene, Novartis, Roche, Almirall, Merck, TEVA; payment for expert testimony from Biogen, Celgene, Novartis, Roche, Almirall, Merck, TEVA; support for attending meetings and/or travel from Biogen, Celgene, Novartis, Roche, Almirall, Merck, TEVA. Participation on a Data Safety Monitoring Board or Advisory Board for Biogen, Celgene, Novartis, Roche, Almirall, Merck, TEVA; Leadership or fiduciary role in other board, society, committee or advocacy group, paid or unpaid for Swiss MS Society Advisory Board. F.D.: Received grants or contracts from Biogen, Roche, Merck, Sanofi Novartis; consulting fees from Alexion, Almirall Biogen, Celgene, Sanofi, Merck, Novartis, Roche; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Biogen, Celgene, Sanofi, Merck, Novartis, Roche; support for attending meetings and/or travel from Biogen, Merck, Sanofi. F.D.P.: Received grants or contracts from Roche, Novartis, Merck, Biogen, Genzyme-Sanofi; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Roche, Novartis, Merck, Biogen, Genzyme-Sanofi, BMS/Celgene, Novartis; support for attending meetings and/or travel from Roche, Novartis, Merck, Biogen, Genzyme-Sanofi, BMS/Celgene, Novartis. Participation on a Data Safety Monitoring Board or Advisory Board for Biogen, BMS/Celgene, Genzyme-Sanofi. R.D.P.: Declares that there is no conflict of interest. C.E.: Received payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Novartis, Teva, Biogen, Genzyme, Sanofi, Almirall. Participation on a Data Safety Monitoring Board or Advisory Board for Novartis, Biogen, Sanofi. E.F.: Received payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Merck, Biogen, Teva; support for attending meetings and/or travel from Sanofi, Teva, Roche. Participation on a Data Safety Monitoring Board or Advisory Board for Celgene, Roche, Merck; Leadership or fiduciary role in other board, society, committee or advocacy group, paid or unpaid as ÖGN Vorstand/Präsidentin. A.G.: Received funding and provision of study materials from Biogen, BMS, Merck, Roche, Schering, Teva; consulting fees from Biogen, BMS, Merck, Roche, Schering, Teva; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Biogen, BMS, Merck, Roche, Schering, Teva. K.G.: Received payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Genzyme, Roche, Biogen, Novartis; support for attending meetings and/or travel including DGN 2019, DGN 2020, AAN 2021. Participation on a Data Safety Monitoring Board or Advisory Board for Siponimod, Ponesimod, Ozanimod. C.G.: Received honoraria for speaking, consulting fees, and research grants from Abbvie, Almirall, Biogen-Idec, Bayer, Celgene, Genzyme, Merck Serono, Novartis, Teva Pharma, Roche. N.G.: Paid consultant, expert, adboard activity for Roche; fees for lectures/trainings/authorships from Biogen; research projects/clin. studies with Biogen, Novartis, Roche, Sanofi/Genzyme. M.G.: Received payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Almirall, Biogen, Celgene, Genzyme, Merck, Novartis, Roche, Sanofi-Aventis and TEVA ratiopharm; support for attending meetings from Bayer, Biogen, Celgene, Genzyme, Merck, Novartis, Roche, Sanofi-Aventis and TEVA ratiopharm. Participation on a Data Safety Monitoring Board or Advisory Board for Almirall, Biogen, Celgene, Genzyme, MedDay, Merck, Novartis, Roche, Sanofi-Aventis, Shire and TEVA ratiopharm; Leadership or fiduciary role in other board, society, committee or advocacy group, paid or unpaid for Austrian MS Treatment Registry. A.H.: Received payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Biogen, Novartis, Celgene, Merck Serono. H.P.H.: Received consulting fees from Bayer, Biogen, Celgene-BMS, MedDay, Merck, Novartis, Roche, TG Therapeutics; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Novartis, Roche. Participation on a Data Safety Monitoring Board or Advisory Board for Novartis, Hoffmann-La Roche. F.H.: Received grants or contracts from Merck; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Biogen, Sanofi, Novartis. Participation on a Data Safety Monitoring Board or Advisory Board for Sanofi, Biogen. O.H.: Received grants or contracts from Biogen, Novartis, Sanofi; consulting fees from Merck, Novartis, Roche; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Alexion, Biogen, Merck, Novartis, Roche, Sanofi; support for attending meetings from Bayer, Biogen, Celgene. Participation on a Data Safety Monitoring Board or Advisory Board for Biogen, Celgene, Merck, Novartis, Roche, Sanofi; Leadership or fiduciary role in other board, society, committee or advocacy group, paid or unpaid as Ärztlicher Beirat, Deutsche Multiple Sklerose Gesellschaft Brandenburg (unpaid). Receipt of equipment, materials, drugs, medical writing, gifts, or other services from Merck, Novartis. B.K.: Received payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Biologix, Biogen, Merck, Sanofi, BMS, Novartis. Participation on a Data Safety Monitoring Board or Advisory Board for Biogen, Merck, Sanofi, Roche, Janssen, BMS, Novartis. C.K.: Received grants or contracts from Deutsche Forschungsgemeinschaft (DFG), European Commission, Bundesministerium für Bildung und Forschung (BMBF), Merck Serono GmbH, Biogen GmbH, Roche Pharma GmbH; consulting fees from Alexion, Biogen, Bristol Myers Squibb, Daiichi Sankyo, Merck Serono, Mylan/Viatris, Novartis, Pfizer, Roche, Sanofi-Aventis, Stada, Teva; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Alexion, Almirall, Amgen, Amicus, Bayer, Biogen, Biotronik, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, CSL Behring, Daiichi Sankyo, Desitin, Eisai, Ever Pharma, GE Healthcare, MedDay Pharmaceuticals, Merck Serono, Mylan/Viatris, Novartis, Pfizer, Roche, Sanofi-Genzyme, Siemens, STADA, Stago, Teva; support for attending meetings and/or travel from Biogen, Merck Serono, Teva, Roche, Sanofi-Aventis, Alexion. Participation on a Data Safety Monitoring Board or Advisory Board for Alexion, Biogen, Bristol Myers Squibb, Daiichi Sankyo, Merck Serono, Mylan/Viatris, Novartis, Pfizer, Roche, Sanofi-Aventis, Stada, Teva. Stock or stock options with Biontec, Sanofi. L.K.: Received grants or contracts from the German Research Foundation, the IZKF Münster, IMF Münster, Biogen, Immunic AG, Novartis, Merck Serono; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Bayer, Biogen, Genzyme, Grifols, Merck Serono, Novartis, Roche, Santhera, Teva; support for attending meetings and/or travel from Alexion, Bayer, Biogen, Genzyme, Grifols, Janssen, Merck Serono, Novartis, Roche, Santhera, Teva. Participation on a Data Safety Monitoring Board or Advisory Board for Alexion, Genzyme, Janssen, Merck Serono, Novartis, Roche. V.I.L.: Received payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Novartis, Teva, Biogen, Merck; support for attending meetings and/or travel from Teva, Novartis. F.L.: Received consulting fees from Almirall, Actelion, Biogen-Idec, Celgene-BMS, MedDay, Merck Serono, Novartis, Octapharm, Pfizer, Roche, Sanofi-Genzyme, Santhera, Schering, Teva-Ratiopharm; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Almirall, Actelion, Biogen-Idec, Celgene-BMS, MedDay, Merck Serono, Novartis, Octapharm, Pfizer, Roche, Sanofi-Genzyme, Santhera, Schering, Teva-Ratiopharm; payment for expert testimony and support for attending meetings and/or travel from Almirall, Actelion, Biogen-Idec, Celgene-BMS, MedDay, Merck Serono, Novartis, Octapharm, Pfizer, Roche, Sanofi-Genzyme, Santhera, Schering, Teva-Ratiopharm. V.L.: Declares that there is no conflict of interest. J.D.L.: Received funding, provision of study materials from Swiss National Science Foundation (31003A_169664) and the German Research Foundation (SFB-CRC128); grants or contracts from Swiss National Science Foundation (31003A_169664) and the German Research Foundation (SFB-CRC128); consulting fees from Abbvie, Alexion, Argenx, Biogen, Merck, Novartis, Roche, Sanofi; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Abbvie, Alexion, Argenx, Biogen, Merck, Novartis, Roche, Sanofi; support for attending meetings and/or travel from Merck. Participation on a Data Safety Monitoring Board or Advisory Board for Merck, Roche. A.L.: Received consulting fees from Roche, Novartis, Biogen, Almirall, Merck, Celgene, Merck; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Novartis, Biogen, Almirall, Merck; support for attending meetings and/or travel from Celgene, Roche, Biogen. Patents planned, issued, or pending. Named on a patent of the University of Zurich on the use of autologous peptide coupled blood cells for treatment of MS. Leadership or fiduciary role in other board, society, committee or advocacy group, paid or unpaid as Member of the Advisory Board of the Swiss MS Society. Stock or stock options as Co-Founder and shareholder of Cellerys. S.G.M.: Received payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Biogen, Novartis, Sanofi, BMS, Merck Serono, Almirall, Alexion, TEVA, Celgene, Roche; support for attending meetings and/or travel from Biogen, Novartis, Merck. Participation on a Data Safety Monitoring Board or Advisory Board for Biogen, Novartis, Merck. U.M.L.: Received grants or contracts from Almirall, Bayer Health Care, Biogen-Idec, Boehringer Ingelheim, Genzyme, Med Day, Merck Sono, Novartis, Pfizer, Roche, Teva, UCB, Eisai, Mylan, Sanofi-Genzyme, Shire, Akcea, Alexion, Alnylam, Behring CSL, Kedrion; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Roche, Novartis, Alexion, Pfizer, Nordd. Chefärzte, Merck Sereno, Biogen, Lilly, RG Digital, Celgene, Advisory Board Fa. Roche, Streamedup NeuroLive. M.P.: Received consulting fees from Novartis; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Novartis; support for attending meetings and/or travel from Novartis. Participation on a Data Safety Monitoring Board or Advisory Board for Roche. P.R.: Received consulting fees from Merck, Sanofi, Roche, Teva; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Merck, Sanofi, Roche, BMS, Teva, Celgene, Novartis. S.Sch.: Received consulting fees from Biogen, Merck Serono, Novartis, Roche; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from BayerVital, Biogen, Merck Serono, Novartis, Sanofi, Roche, Teva; support for attending meetings and/or travel from BayerVital, Biogen, Merck Serono, Novartis, Sanofi, Roche, Teva. Participation on a Data Safety Monitoring Board or Advisory Board for Biogen, Merck Serono, Novartis, Roche. H.T.: Received grants or contracts from BMBF, DMSG, DZNE, GBS-Stiftung, Chemische Fabrik Karl Bucher, Biogen, Genzyme-Sanofi, Merck, Novartis, Roche; Consulting fees from Labor Gärtner, Reck; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Alexion, Bayer, Biogen, Celgene, Genzyme-Sanofi, Merck, Novartis, Roche, Teva. Participation on a Data Safety Monitoring Board or Advisory Board for Alexion, Bayer, Biogen, Celgene, Genzyme-Sanofi, Merck, Novartis, Roche, Teva; Leadership or fiduciary role in other board, society, committee or advocacy group, paid or unpaid with DGLN (executive board). F.W.: Received payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Pfizer, Merk; support for attending meetings and/or travel from Novartis, Bayer. M.S.W.: Declares that there is no conflict of interest. U.K.Z.: Received grants or contracts from BMBF, BMWi, EU; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Alexion, Almirall, Bayer, Biogen, Celgene, Genzyme, Merck, Novartis, Roche, Teva. Participation on a Data Safety Monitoring Board or Advisory Board for Alexion, Biogen, Celgene, Genzyme, Janssen, Merck, Roche. T.Z.: Received grants or contracts from Novartis, Roche, Teva, Celgene-BMS, Sanofi, Biogen, Merck, Alexion, Janssen-Cilag; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Novartis, Roche, Teva, Celgene-BMS, Sanofi, Biogen, Merck, Alexion. Participation on a Data Safety Monitoring Board or Advisory Board for Roche, Celgene-BMS, Sanofi, Biogen, Merck, Novartis; Leadership or fiduciary role in other board, society, committee or advocacy group, paid or unpaid as DMSG Membership, Participation Brain Health Initiative, EAN Membership, DGN Membership. F.Z.: Participation in a scientific advisory board or lecturing activity for Novartis, Roche, Celgene, Janssen, Novartis Pharma, Janssen Pharmaceutica, Sandoz International, F. Hoffmann–La Roche; research projects/conduction of clinical studies for Precisis, UCB, SK Life Science, Biogen, Grünenthal, Actelion. Ownership interests in the health care sector, that is, Patent application Cytokine derivatives.

Figures

Figure 1.
Figure 1.
Disease-modifying therapy of MS. Available drugs are listed alphabetically, not by strength or preference. Scheme updated based on the KKNMS Scheme, Aktuelle Neurologie 2014. Azathioprine is formally approved but rarely applied (second choice). Mitoxantrone formally approved here as well as in highly active RRMS but rarely applied due to the unfavorable side-effect profile and the cumulative maximum dose (second choice). Natalizumab: both i.v. and s.c.; especially in case of HPyV-2 (JCV) antibody positivity [HPyV-2 (JCV) Ab ⩾ 0.9 HPyV-2 (JCV) Ab titer] risk stratification is essential due to PML risk! High risk for PML after (a) prior immunosuppression, (b) ⩾18 months of continuous therapy, and with (c) positive HPyV-2 (JCV) Ab status. Interferons: interferon-b-1a i.m., interferon-b-1a s.c., interferon-b-1b s.c., pegylated interferon-b-1a s.c./i.m. Glatiramer acetate includes other glatiramoids. Decisions on type of therapy (as well as therapy concept) depend on the level of disease activity and severity; thus first- and second-line therapies are included here. For explanations on specific multiple sclerosis types, see also Box 1.

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